Study objectives: To examine predictors of sleep-disordered breathing in patients with cystic fibrosis (CF) and moderate-to-severe lung disease using a comprehensive evaluation of both sleep and daytime function. Design: Cross-sectional analysis of sleep studies, lung function, respiratory muscle strength, and evening and morning arterial blood gas measurements in patients with stable CF. A questionnaire addressing sleep quality was administered. Forward stepwise regression analysis was used to identify, the parameters that best predict sleep-related desaturation, hypercapnia, and respiratory, disturbance. Setting: Sleep investigation unit and lung function laboratory. Patients: Thirty-two patients with CF and FEV1 < 65% predicted, in stable clinical condition. Patients were aged 27 +/- 8 years (mean +/- 1 SD) with FEV1 of 36 +/- 10% predicted, evening Pao(2) of 68 +/- 8 mm Hg, and PaCO2 of 43 +/- 5 mm Hg. Results: Evening Pao(2) (p < 0.0001) and morning PaCO2 (p < 0.01) were predictive of the average minimum oxyhemoglobin saturation per 30-s epoch of sleep (r(2) = 0.74; p < 0.0001). Evening Pao(2) (p < 0.001) was predictive of the rise in transcutaneous carbon dioxide (TeCO2) seen from non-rapid eve movement (NREM) to rapid eye movement (REM) sleep (r(2) = 0.37; p < 0.001). In addition, there was some relationship between expiratory respiratory muscle strength and the REM respiratory disturbance index (r(2) = 0.22; p < 0.01). Conclusion: Evening Pao2 was found to contribute significantly to the ability to predict both sleep-related desaturation and the rise in TeCO2 from NREM sleep to REM sleep in thins subgroup of patients with CF.